Blood coagulation, also known as thrombogenesis, is an important physiological process that prevents the excessive loss of blood from the body in the events of injury and tissue damage. The process of coagulation is orchestrated largely by the different proteins present in the plasma, in particular, those along a complex cascade of enzymatic reactions, known as the blood coagulation cascade. While physiological formation of clots (thrombus) is critical for hemostasis and preservation of blood volume, abnormal and pathogenic thrombosis is related to a number of cardiovascular diseases [Peter, K. and G. Y. Lip, Thromb Haemost, 2010. 103(5):875-6].
The blood coagulation cascade is a crucial process for regulating thrombosis and can be divided into three pathways: intrinsic, extrinsic and common pathway [Johan, V. and C. Loke, Dis Mon, 2012. 58(8):421-3]. Protease such as Factor X (FX), thrombin and tissue factor, which participate in the extrinsic and common pathways are the prevailing drug targets for anti-thrombotic design, as the inhibition of these proteins' functions can easily achieve high inhibitory potency in clot formation in blood [Danalev, D., Mini Rev Med Chem, 2012. 12(8): p. 721-30]. However, the current approved drugs targeting these targets are all associated with high risks of excessive bleeding when used for anti-thrombotic purpose.
Therefore, improved anti-coagulent compositions and methods are needed to minimize the most common and severe side effects of excessive bleeding seen in many of the current anti-coagulants seen on the market.